Overexpression of tumor necrosis factor-α increases production of hydroxyl radical in murine myocardium

Yoji Machida, Toru Kubota, Natsumi Kawamura, Hajime Funakoshi, Tomomi Ide, Hideo Utsumi, Yun You Li, Arthur M. Feldman, Hiroyuki Tsutsui, Hiroaki Shimokawa, Akira Takeshita

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Transgenic (TG) mice with cardiac-specific overexpression of tumor necrosis factor-α develop congestive heart failure with myocardial inflammation. The purpose of this study was to investigate the effects of tumor necrosis factor-α on reactive oxygen species (ROS) in this mouse model of cardiomyopathy. Myocardial production of hydroxyl radical detected by electron spin resonance spectroscopy was significantly increased in TG. Myocardial expression of Mn-SOD was significantly decreased in TG, whereas that of Cu,Zn-SOD was unaltered. Myocardial expression of catalase was unchanged, whereas that of glutathione peroxidase was significantly increased, in TG. Histological analysis revealed that macrophages and CD4-positive lymphocytes were increased in TG myocardium. To investigate whether these infiltrating inflammatory cells were the source of ROS, we treated TG mice with cyclophosphamide for 7 days. Although cyclophosphamide significantly suppressed the infiltration of inflammatory cells, it did not diminish the production of hydroxyl radical in TG myocardium. Damaged myocytes, but not infiltrating inflammatory cells, may be the source of ROS in TG.

Original languageEnglish
Pages (from-to)H449-H455
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number2 53-2
DOIs
Publication statusPublished - 2003 Feb 1

Keywords

  • Cytokine
  • Heart failure
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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